Despite recent work in the cancer treatment against the MTHFD2 enzyme, still limited wet lab and molecular modeling attempts have been made to discover the effective inhibitors against the allosteric site of the MTHFD2 enzyme, which explain the importance and novelty of the current work.We present the in silico drug designing methods where structure-based tools were compiled with the molecular dynamics and free energy calculations to search for the inhibitors that can bind in the allosteric binding domain of the MTHFD2 enzyme. Here, MTHFD2 is linked to cancer.